Hepatocellular carcinoma (HCC) or liver cancer is one of the most common cancers and one of the leading causes of death worldwide (1). HCC arises most commonly in cirrhotic livers following infection with hepatitis B virus (HBV) or hepatitis C virus (HCV) (2, 3). Indeed, liver cirrhosis is an important cause of death and a major risk factor for development of HCC, and 60-80% of HCC had been preceded by cirrhosis (4). Therefore, screening cirrhosis populations for early stage HCC can reduce mortality. Various imaging techniques are used to diagnose HCC, e.g. ultrasonography, computed tomographic scanning and magnetic resonance imaging (5, 6). However, these techniques cannot distinguish benign hepatic lesions, such as dysplastic nodules and cirrhotic macronodules, from HCC. For a long time serum tumor markers have been used as an effective method for detecting malignant tumors (7-9), and they could be valuable supplements to ultrasonography and computed tomography in the diagnosis of HCC (10-12). Serum AFP (alpha-fetoprotein) is the only serum marker that is widely used for diagnosis and follow-up of HCC (13, 14). A recent meta-analysis showed that the sensitivity and specificity of AFP varied widely, and that these variations could not be entirely attributed to the threshold effect of the different cutoff levels used (15). Other improved serological markers, whether used alone or together with others, are needed for early detection of HCC. Most serum N-linked glycoproteins are synthesized by the liver and B-lymphocytes. Any changes in serum total N-glycans could reflect alteration of liver or B-lymphocyte physiology. Because the sugar chains of glycoproteins are important for maintaining the ordered “social behavior” of differentiated cells in multicellular organisms, alterations in the sugar chains contribute to the molecular basis of abnormalities such as invasion of tumor cells into the surrounding tissues and their metastasis. Alterations in the N-linked sugar chains are indeed found in various tumors (6, 16-18). Until recently, the use of glycomics in diagnosis has been limited by the lack of appropriate analytical techniques, but at least in the case of the serum N-glycome this has been overcome (19, 20). In the present invention we evaluated the use of blood serum N-glycan fingerprinting as a tool for diagnosis of hepatocellular carcinoma (HCC) in patients with cirrhosis induced by hepatitis B virus. In particular, we found that branch alpha(1,3)-fucosylated glycans were more abundant in HCC patients than in cirrhosis patients, fibrosis patients and healthy blood donors, whereas bisecting GlcNac (N-acetylglucosamine)-core alpha (1,6)-fucosylated glycans were elevated in cirrhosis patients. The concentration of these two glycan-forms and the log ratio thereof (renamed as GlycoHCCTest) was associated with the tumor stage of liver cancer.